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Activation of protease‐activated receptor‐4 inhibits the intrinsic excitability of colonic dorsal root ganglia neurons
Author(s) -
Karanjia R.,
Spreadbury I.,
Bautistacruz F.,
Tsang M. E.,
Vanner S.
Publication year - 2009
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2009.01353.x
Subject(s) - rheobase , receptor , patch clamp , nociception , excitatory postsynaptic potential , chemistry , dorsum , distal colon , neuroscience , electrophysiology , medicine , pharmacology , biology , endocrinology , biochemistry , anatomy
Abstract The antinociceptive mechanism underlying protease‐activated receptor‐4 (PAR 4 ) activation was studied in Fast Blue‐labelled dorsal root ganglia (DRG) neurons from mouse colon which expressed transcript for PAR 4 . Whole cell perforated patch clamp recordings were obtained from these neurons and the effects on neuronal excitability of PAR 4 activating peptides (AP) and reverse peptides (RP) were examined. A 3‐min application of PAR 4 ‐AP (100 μ mol L −1 ) markedly suppressed the number of action potential discharged at twice rheobase for up to 60 min. PAR 4 ‐RP had no effect. PAR 4 application suppresses the excitatory effects of PAR 2 . These findings demonstrated that activation of PAR 4 on colonic DRG neurons suppresses their excitability, suggesting these receptors could provide important targets for modifying pain in colonic GI disorders such as IBS and IBD.